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Shabaldin A.V.

Research Institute for Complex Issues of Cardiovascular Diseases

Sinitskaya A.V.

Research Institute for Complex Issues of Cardiovascular Diseases

Shmulevch S.A.

Research Institute for Complex Issues of Cardiovascular Diseases

Ponasenko A.V.

Research Institute for Complex Issues of Cardiovascular Diseases

The role of maternal folate cycle gene polymorphisms: contribution to susceptibility to congenital heart disease

Authors:

Shabaldin A.V., Sinitskaya A.V., Shmulevch S.A., Ponasenko A.V.

More about the authors

Journal: Russian Journal of Human Reproduction. 2022;28(5): 23‑28

DOI: 10.17116/repro20222805123

Read: 1726 times

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Table of contents

THE ROLE OF MATERNAL FOLATE CYCLE GENE POLYMORPHISMS: CONTRIBUTION TO SUSCEPTIBILITY TO CONGENITAL HEART DISEASE
THE ROLE OF MATERNAL FOLATE CYCLE GENE POLYMORPHISMS: CONTRIBUTION TO SUSCEPTIBILITY TO CONGENITAL HEART DISEASE

To cite this article:

Shabaldin AV, Sinitskaya AV, Shmulevch SA, Ponasenko AV. The role of maternal folate cycle gene polymorphisms: contribution to susceptibility to congenital heart disease. Russian Journal of Human Reproduction. 2022;28(5):23‑28. (In Russ.)
https://doi.org/10.17116/repro20222805123

 
Подписка 2026 Проблемы репродукции (Russian Journal of Human Reproduction)
 
МСФ на ЯМ
Использование инфографики авторами научных работ
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Abstract:

Congenital heart disease (CHD) is one of the leading causes of childhood disability and mortality worldwide. The searching for predictors involved in the CHD pathogenesis including various genes encoding the folate-metabolizing enzymes is a very urgent task for modern biomedicines.

AIM

To study the associations between polymorphism in the MTHFR (C677T), MTHFR (A1298C), MTR (A2756G) and MTRR (A66G) genes and CHD risk.

MATERIAL AND METHODS

179 females having children with CHD (case group) and 103 females having two and more healthy children (control group) were included in the presented study. Genotyping of polymorphic variants in the MTHFR (C677T), MTHFR (A1298C), MTR (A2756G) and MTRR (A66G) genes was performed using real-time PCR. Gene-gene interaction was studied by MDR (Multifactor dimensionality reduction) method.

RESULTS

Two statistically significant models of gene-gene interactions associated with CHD risk were identified. Model A is represented by a combination of two polymorphic variants in the MTHFR (C677T) and MTRR (A66G) genes. Model B is characterized by a combination of all studied polymorphic variants. For both models no significant protective combinations of female genotypes of the studied genes in relation to CHD risk in the next generation were found.

CONCLUSION

The study showed that CHD without chromosomal abnormalities is associated with the combined genotype MTHFR (C677T)*C/T — MTRR (A66G)*A/G; OR 2.15 (95% CI 1.75; 4.96), p=0.01. Moreover, polymorphic variants in the MTHFR (C677T) and MTRR (A66G) genes have a synergistic effect towards sporadic CHD risk in the next generation, while the MTHFR (A1298C) and MTR (A2756G) genes have an antagonistic effect.

Keywords:

folate-metabolizing genes
CHD
homocysteine
folic acid

Authors:

Shabaldin A.V.

Research Institute for Complex Issues of Cardiovascular Diseases

Sinitskaya A.V.

Research Institute for Complex Issues of Cardiovascular Diseases

Shmulevch S.A.

Research Institute for Complex Issues of Cardiovascular Diseases

Ponasenko A.V.

Research Institute for Complex Issues of Cardiovascular Diseases

Received:

30.11.2021

Accepted:

01.07.2022

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References:

  1. Du B, Shi X, Yin C, Feng X. Polymorphisms of methalenetetrahydrofolate reductase in recurrent pregnancy loss: an overview of systematic reviews and meta-analyses. Journal of Assisted Reproduction and Genetics. 2019;36(7):1315-1328. https://doi.org/10.1007/s10815-019-01473-2
  2. Guo QN, Wang HD, Tie LZ, Li T, Xiao H, Long JG, Liao SX. Parental Genetic Variants, MTHFR 677C>T and MTRR 66A>G, Associated Differently with Fetal Congenital Heart Defect. BioMed Research International. 2017;2017:3043476. https://doi.org/10.1155/2017/3043476
  3. Wang HL, Sun L, Zhou S, Wang F. Association between 5,10-methylenetetrahydrofolate, gene polymorphism and congenital heart disease. Journal of Biological Regulators and Homeostatic Agents. 2018; 32(5):1255-1260.
  4. Chrysant SG, Chrysant GS. The current status of homocysteine as a risk factor for cardiovascular disease: a mini review. Expert Review of Cardiovascular Therapy. 2018;16(8):559-565.  https://doi.org/10.1080/14779072.2018.1497974
  5. Chen X, Gao B, Ponnusamy M, Lin Z, Liu J. MEF2 signaling and human diseases. Oncotarget. 2017;8(67):112152-112165. https://doi.org/10.18632/oncotarget.22899
  6. Ebaid H, Bashandy SAE, Abdel-Mageed AM, Al-Tamimi J, Hassan I, Alhazza IM. Folic acid and melatonin mitigate diabetic nephropathy in rats via inhibition of oxidative stress. Nutrition and Metabolism. 2020;17:6.  https://doi.org/10.1186/s12986-019-0419-7
  7. Saperova EV, Vahlova IV. Congenital heart defects in children: prevalence, risk factors, mortality. Voprosy sovremennoj pediatrii. 2017; 16(2):126-133. (In Russ.). https://doi.org/10.15690/vsp.v16i2.1713
  8. Deng C, Deng Y, Xie L, Yu L, Liu L, Liu H, Dai L. Genetic polymorphisms in MTR are associated with non-syndromic congenital heart disease from a family-based case-control study in the Chinese population. Scientific Reports. 2019;9(1):5065. https://doi.org/10.1038/s41598-019-41641-z
  9. Yang Y, Luo Y, Yuan J, Tang Y, Xiong L, Xu M, Rao X, Liu H. Association between maternal, fetal and paternal MTHFR gene C677T and A1298C polymorphisms and risk of recurrent pregnancy loss: a comprehensive evaluation. Archives of Gynecology and Obstetrics. 2016;293(6):1197-1211. https://doi.org/10.1007/s00404-015-3944-2
  10. Khan R, Tang J, Hussain HMJ, Muhammad N, Sun Y, Wang C, Daha Fazla. Association of MTHFR C677T with Idiopathic Recurrent Pregnancy Loss in Anhui Province of China. International Journal of Human Genetics. 2019;19(4):158-164.  https://doi.org/10.31901/24566330.2019/19.04.728
  11. Mazokopakis EE, Papadomanolaki MG. Methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms among Greek women with medical history of recurrent pregnancy loss. Archives of Gynecology and Obstetrics. 2020;302(6):1555-1556. https://doi.org/10.1007/s00404-020-05485-7
  12. Tsepokina AV, Khutornaya MV, Shabaldin AV, Panasenko AV. The role of gene TREM-1 at children who have operation congenital heart diseases. Translyacionnaya medicina. 2019;6(4):5-12. (In Russ.).
  13. Lou XY, Chen GB, Yan L, Ma JZ, Zhu J, Elston RC, Li MD. A generalized combinatorial approach for detecting gene-by-gene and gene-by-environment interactions with application to nicotine dependence. American Journal of Human Genetics. 2007;80(6):1125-1137. https://doi.org/10.1086/518312
  14. Virani SS, Alonso A, Benjamin EJ, Bittencourt MS, Callaway CW, Carson AP, Chamberlain AM, Chang AR, Cheng S, Delling FN, Djousse L, Elkind MSV, Ferguson JF, Fornage M, Khan SS, Kissela BM, Knutson KL, Kwan TW, Lackland DT, Lewis TT, Lichtman JH, Longenecker CT, Loop MS, Lutsey PL, Martin SS, Matsushita K, Moran AE, Mussolino ME, Perak AM, Rosamond WD, Roth GA, Sampson UKA, Satou GM, Schroeder EB, Shah SH, Shay CM, Spartano NL, Stokes A, Tirschwell DL, VanWagner LB, Tsao CW; American Heart Association Council on Epidemiology and Prevention Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2020 Update: A Report from the American Heart Association. Circulation. 2020;141(9):139-596.  https://doi.org/10.1161/CIR.0000000000000757
  15. Lievers KJ, Boers GH, Verhoef P, den Heijer M, Kluijtmans LA, van der Put NM, Trijbels FJ, Blom HJ. A second common variant in the methylenetetrahydrofolate reductase (MTHFR) gene and its relationship to MTHFR enzyme activity, homocysteine, and cardiovascular disease risk. Journal of Molecular Medicine. 2001;79(9): 522-528.  https://doi.org/10.1007/s001090100253
  16. Elizabeth KE, Praveen SL, Preethi NR, Jissa VT, Pillai MR. Folate, vitamin B12, homocysteine and polymorphisms in folate metabolizing genes in children with congenital heart disease and their mothers. European Journal of Clinical Nutrition. 2017;71(12):1437-1441. https://doi.org/10.1038/ejcn.2017.135
  17. Yu Y, Jia C, Shi Q, Zhu Y, Liu Y. Hyperhomocysteinemia in men with a reproductive history of fetal neural tube defects: Three case reports and literature review. Medicine. 2019;98(2):e13998. https://doi.org/10.1097/MD.0000000000013998
  18. van Beynum IM, Kapusta L, den Heijer M, Vermeulen SH, Kouwenberg M, Daniëls O, Blom HJ. Maternal MTHFR 677C>T is a risk factor for congenital heart defects: effect modification by periconceptional folate supplementation. European Heart Journal. 2006; 27(8):981-987.  https://doi.org/10.1093/eurheartj/ehi815
  19. Wang L, Yang B, Zhou S, Gao H, Wang F, Zhou J, Wang H, Wang Y. Risk factors and methylenetetrahydrofolate reductase gene in congenital heart disease. Journal of Thoracic Disease. 2018;10(1):441-447.  https://doi.org/10.21037/jtd.2017.12.08
  20. Li P, Huang L, Zheng Y, Pan X, Peng R, Jiang Y, Finnell RH, Li H, Qiao B, Wang HY. A missense mutation in TCN2 is associated with decreased risk for congenital heart defects and may increase cellular uptake of vitamin B12 via Megalin. Oncotarget. 2017;8(33): 55216-55229. https://doi.org/10.18632/oncotarget.19377
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